This invention relates to the stabilization, especially for the prevention of decomposition during long-term storage under dry conditions, of estrogens alkali metal sulfates.
Estrogen sulfates are contained in the urine of pregnant mares in the form of their water-soluble sodium salts. A mixture of these naturally occurring conjugated estrogens, consisting primarily of the sodium salts of the 3-hemisulfates of estrone, equilin, and equilenin, as well as the 17-dihydro derivatives thereof, viz., 17.alpha.-estradiol, 17.alpha.-equilol, and 17.alpha.-equilenol, is obtained by extraction and is utilized in therapy mainly for mitigating the complaints connected with the climacteric.
However, such mixtures do not always have the same composition and, therefore, they are standarized by the addition of synthetically prepared salts of other estrogen sulfates, e.g., estrone sulfate.
It is also possible to replace the mixture isolated from the urine completely by a synthetic mixture of sodium salts of the estrogen sulfates.
However, the alkali metal salts of these synthetic estrogen sulfates have the disadvantage that they are unstable in a pure, dry condition and decompose with the formation of the corresponding estrogen and alkali hydrogen sulfate.
A number of suggestions have been advanced to improve the stability of these compounds, for example by additions of the urine from mares (Canadian Pat. Nos. 691,988 and 922,627), of N-methylglucamine (U.S. Pat. No. 3,024,257), of other substituted amines (German Unexamined Laid-Open Application DOS No. 1,918,291), of amino acids (DOS No. 1,937,519), or by the preparation of the salts of quaternary ammonium bases (German Published Application DAS No. 1,032,740) in place of alkali metal salts of the estrogen sulfates.
However, these processes are technically complicated, utilize relatively expensive and/or nonphysiological additives, or lead to compounds which are soluble in water only with great difficulties.
It is an object of the present invention to provide a simple and physiologically acceptable stabilizer which is effective over an unlimited period of time.